1. Field of the Invention
The invention relates to the use of multiple markers, detected using RT-PCR to detect metastasis of breast cancer. The invention further relates to the use of multiple markers to determine cancer staging and prognosis.
2. Background Art
Breast cancer remains a leading cause of cancer death among American women [1]. When staging a patient with breast cancer, lymph node status continues to be the most valuable predictor of prognosis. An inverse relationship exists between the number of lymph nodes positive for cancer and the patient's survival [1,2]. The standard method for evaluating the lymph nodes of patients with breast cancer is histologic analysis of hematoxylin and eosin stained sections from axillary lymph nodes within the ipsilateral lymph node basin. Axillary lymph node (ALN) status in breast cancer patients remains the single most important predictor of outcome. However, as many as 30% of patients with pathologically negative lymph nodes ultimately develop recurrent cancer, suggesting that current methods are inadequate for identifying micrometastatic disease [3].
Serial sectioning of these nodes combined with the use of immunohistochemical stains can demonstrate micrometastases in up to 25% of nodes which were "negative" during the routine histopathologic examination process [4,5]. Furthermore, it has been suggested retrospectively that these patients with occult micrometastatic disease have a poorer prognosis [5]. Despite the valuable information it provides, serial sectioning and staining is too cumbersome and costly to be performed as a routine.
Given the significant incidence of missed metastases by routine pathology (and current 30% recurrence rate in node-negative breast cancer patients) a more sensitive method of detecting metastases would be of clear benefit to the clinician making treatment decisions. The present RT-PCR technology applied as a multimarker screening panel is significantly more sensitive and cost-effective method to detect occult axillary lymph node micrometastases in breast cancer patients.